Clinical diagnosis and management of pancreatic cancer: Markers, molecular mechanisms, and treatment options

Abstract

Pancreatic cancer (PC) is the third-leading cause of cancer deaths. The overall 5-year survival rate of PC is 9%, and this rate for metastatic PC is below 3%. However, the PC-induced death cases will increase about 2-fold by 2060. Many factors such as genetic and environmental factors and metabolic diseases can drive PC development and progression. The most common type of PC in the clinic is pancreatic ductal adenocarcinoma, comprising approximately 90% of PC cases. Multiple pathogenic processes including but not limited to inflammation, fibrosis, angiogenesis, epithelial-mesenchymal transition, and proliferation of cancer stem cells are involved in the initiation and progression of PC. Early diagnosis is essential for curable therapy, for which a combined panel of serum markers is very helpful. Although some mono or combined therapies have been approved by the United States Food and Drug Administration for PC treatment, current therapies have not shown promising outcomes. Fortunately, the development of novel immunotherapies, such as oncolytic viruses-mediated treatments and chimeric antigen receptor-T cells, combined with therapies such as neoadjuvant therapy plus surgery, and advanced delivery systems of immunotherapy will improve therapeutic outcomes and combat drug resistance in PC patients. Herein, the pathogenesis, molecular signaling pathways, diagnostic markers, prognosis, and potential treatments in completed, ongoing, and recruiting clinical trials for PC were reviewed.

Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

“…In addition, activating the FAK signaling pathway in PDAC cells by CAF-derived β1-integrins can promote their clonogenic growth [129]. Furthermore, FAK inhibitors or their combination with immune checkpoint inhibitors can inhibit extracellular matrix production and the cell migration of CAFs and display antitumor effects in PDAC models [131,132]. Treatment with the FAK inhibitor VS-4718 decreased collagen production by decreasing the number of SMAexpressing fibroblasts and inhibiting the TGF-β/SMAD signaling pathway in PDAC [133].…”

NIR Fluorescent/Photoacoustic Bimodal Imaging of Ferroptosis in Pancreatic Cancer Using Biothiols-Activable Probes

“…Its distinct tumor microenvironment, marked by hypovascular and hyperdense extracellular matrix, poses challenges for effective drug delivery to the tumor center. , Consequently, most PDAC patients resort to palliative treatments as conventional approaches such as chemotherapy, radiation therapy, and immunotherapy often yield limited responses in symptom alleviation and survival prolongation. Despite advances in the progression of new treatments of PDAC, the situation is still very severe that the 1-year mortality rate of PDAC patients is still high, and the overall 5-year survival rate of PDAC patients is only about 9% . Thus, innovative therapeutic strategies for PDAC are urgently needed.…”

“…Despite advances in the progression of new treatments of PDAC, the situation is still very severe that the 1year mortality rate of PDAC patients is still high, and the overall 5-year survival rate of PDAC patients is only about 9%. 3 Thus, innovative therapeutic strategies for PDAC are urgently needed. Excitingly, recent studies demonstrate that ferroptosis modulation is a powerful therapeutic option for PDAC.…”

The Multikinase Inhibitor AD80 Induces Mitotic Catastrophe and Autophagy in Pancreatic Cancer Cells

“…Pancreatic cancer is one of the most lethal human malignancies presenting a 5-year survival rate of less than 10% [1], indicating that current therapeutic interventions for this cancer are far from satisfactory [2]. In recent years, significant advances in understanding the molecular complexity of the development and progression of pancreatic cancer opened the opportunity for new treatments [3].…”

“…In recent years, significant advances in understanding the molecular complexity of the development and progression of pancreatic cancer opened the opportunity for new treatments [3]. Surgical resection is a curable therapy for pancreatic cancer patients with early stages of the disease, and gemcitabine (alone or in combination with target therapies) is a backbone drug for locally advanced and metastatic pancreatic cancer patients [2,4]. The use of systemic combination chemotherapies (i.e., 5-fluorouracil, folinic acid, irinotecan, and oxaliplatin, or/and gemcitabine plus nab-paclitaxel) has gained increasing prominence in the treatment of this type of tumor.…”